The procedures developed in this laboratory, which are based on operant conditioning principles, have proved to be successful in the establishment of self-administration of drugs from several major classes in both rats and rhesus monkeys. Drugs such as etonitazene, pentobarbital, and phencyclidine serve as reinforcers for monkeys since they are self-administered at rates and volumes in excess of vehicle (water) values. These are the only demonstrations of drugs (other than ethanol) serving as reinforcers orally for non-human primates. The proposed research is designed to further study conditions under which drugs serve as reinforcers such as schedule of reinforcement, feeding condition, drug concentration and training procedure. Other questions that will be investigated will be whether there is tolerance and/or physical dependence to the self-administered drugs. We will also study the interactions among the variables and the relative importance of each variable will be assessed with respect to its ability to control drug-reinforced behavior. There are at least three significant outcomes of the proposed research: 1) an increase in the generality of our infrahuman model of oral drug self-administration will result from testing other drugs under a variety of conditions; 2) an increasing body of knowledge will be available and may be relevant to our understanding of human drug dependence; 3) the refinement of the oral method for establishing drugs as reinforcers will result in a reliable and long term preparations that later could be used to study many other aspects of drug abuse such as drug interactions (choice procedures), toxicity, and pretreatment with pharmacological agents.